title: Enantioselective synthesis of tranylcypromine analogues as lysine demethylase (LSD1) inhibitors.
abstract: Asymmetric cyclopropanation of styrenes by tert-butyl diazoacetate followed by ester hydrolysis and Curtius rearrangement gave a series of tranylcypromine analogues as single enantiomers. The o,- m- and p-bromo analogues were all more active than tranylcypromine in a LSD1 enzyme assay. The m- and p-bromo analogues were micromolar growth inhibitors of the LNCaP prostate cancer cell line as were the corresponding biphenyl analogues prepared from the bromide by Suzuki crosscoupling.
authors.affiliation: School of Chemistry, University of Southampton, Southampton SO17 1BJ, United Kingdom.
authors.forename: Hanae
authors.initials: H
authors.lastname: Benelkebir
authors.forename: Christopher
authors.initials: C
authors.lastname: Hodgkinson
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Duriez
authors.forename: Annette L
authors.initials: AL
authors.lastname: Hayden
authors.forename: Rosemary A
authors.initials: RA
authors.lastname: Bulleid
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Crabb
authors.forename: Graham
authors.initials: G
authors.lastname: Packham
authors.forename: A
authors.initials: A
authors.lastname: Ganesan
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001966:Bromine / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D056466:Histone Demethylases / Q000037:antagonists & inhibitors*; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D013237:Stereoisomerism; D014191:Tranylcypromine / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D014191:Tranylcypromine; D056466:Histone Demethylases; D001966:Bromine